Cysteine/glutathione deficiency: A significant and treatable corollary of disease

• Type of Material: Book Chapter
• Authors: Pietro Ghezzi, Brighton and Sussex Medical School; Kevin V. Lemley, Stanford University; James P. Andrus, Memorial Hospital; Stephen C. De Rosa, Fred Hutchinson Cancer Research Center; Ame Holmgren, Karolinska Institutet; Dean Jones, Emory University; Farook Jahoor, Baylor College of Medicine; Richard Kopke, Hough Ear Institute; Ian Cotgreave, Karolinska Institutet; Teodoro Bottiglieri, Baylor University Medical Center at Dallas; Neil Kaplowitz, Los Angeles County USC Medical Center; Hajime Nakamura, Kyoto University; Frank Staal, Erasmus Universiteit Rotterdam; Stephen W. Ela, Venture Science Consulting; Kondala R. Atkuri, Stanford University; Rabindra Tirouvanziam, Emory University; Kartoosh Heydari, Stanford University; Bita Sahaf, Stanford University; Andrew Zolopa, Stanford University; Richard Eugene Frye, University of Arizona College of Medicine – Phoenix; John J. Mantovani, Stanford University; Leonard A. Herzenberg, Stanford University; Leonare A. Herzenberg, Stanford University
• Language: English
• Date: 2018-11-01
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © Springer Nature Singapore Pte Ltd. 2019
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/978-981-10-5311-5_20
• Title of Journal or Parent Work: The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine
• Start Page: 349
• End Page: 386
• Grant/Funding Information: Studies presented here were supported in part by a grant (CA-42509) from the National Cancer Institute of the US National Institutes of Health.
• Keywords: Randomized Placebo-controlled Trial (RPCTs); Cysteine Requirement; Cysteine Supply; APAP Toxicity; APAP Overdose

Abstract

Glutathione (GSH) deficiency may play a pivotal role in a variety of apparently unrelated clinical conditions and diseases. Orally administered N-acetylcysteine (NAC), which replenishes the cysteine required for GSH synthesis, has been tested in a large number of randomized placebo-controlled trials involving these diseases and conditions. This chapter focused on developing a base of evidence suggesting that NAC administration improves disease by increasing cysteine and/or GSH in a variety of diseases, thereby implying a significant role for GSH deficiency in the clinical basis of many diseases. To develop this base of evidence, we systematically selected studies which considered the hypothesis that the therapeutic efficacy for NAC is an indication that cysteine and/or GSH deficiency is a pathophysiological part of the diseases studied. In this manner we focus this chapter on explaining the biological mechanisms of NAC therapy in a wide variety of disorders and demonstrate its ubiquitous role in improving disease that involves disrupted GSH and/or cysteine metabolism.